In this study of endothelial injury and regeneration in large arteries, and its consequences, we are examining (1) the origin of new, regenerating endothelial cells; (2) factors controlling the rate of regeneration, and (3) factors involved in the development of arterial intimal thickening. We are exploiting a recently devised model (Fishman, Ryan and Karnovsky, Lab. Invest. 32: 339, 1975), in which a localized segment of rat carotid artery is denuded of endothelium (without causing detectable injury to the underlying media) by passing a stream of dry air along the lumen of the vessel. The origin of new endothelium is examined by observing the pattern of regrowth, and by kinetic studies using autoradiography. The development of intimal characteristics of the component cells, and the extent of plasma protein and macromolecular penetration from the lumen into this area. The effect of drugs, stress, diet and other manipulations on the degree of endothelial regeneration and intimal proliferation are being assessed. It has been found that heparin has a marked suppressive effect on smooth muscle cell (myo-intimal) proliferation, and mechanism of this action is being sought in in-vivo and in-vitro systems.